Program Director/Principal Investigator (Last, First, Middle): PROJECT SUMMARY Our long-term goal is to understand the neural mechanisms of visual processing early in the cortical pathway. To this end we record from rhesus macaque visual cortex using a combination of intrinsic-signal optical imaging and electrophysiology while the animals are engaged in visual form processing tasks. The goal of the current project is two-fold. We propose to study a novel stimulus-independent anticipatory haemodynamic signal that we observed earlier in alert macaque V1 (primary visual cortex). Through this process we also propose to better understand the physiological basis of neuroimaging signals including fMRI. This project derives from our recent discovery that haemodynamic signals in alert monkey V1 have two distinct components. One component is predictable by visual input and associated V1 neuronal activity. The other component - of comparable strength - is a hitherto unknown haemodynamic signal marking task anticipation. It reflects an arterial pumping mechanism bringing fresh blood to cortex in anticipation of predicted visual events. Electrode recordings conducted simultaneously with the optical imaging showed that this novel haemodynamic signal is not driven by local V1 neuronal activity, in dramatic contrast to visually evoked responses obtained from the same recording sites. We hypothesize that the anticipatory stimulus-independent haemodynamic signal is a mechanism of predictive arousal. We propose to test this hypothesis by characterizing the anticipatory and visually evoked signals, and their interaction, and asking if the anticipatory signal can modulate visually evoked responses and behavior. Our finding of the novel haemodynamic signal also challenges current understandings of neuroimaging signals, notably functional magnetic resonance imaging (fMRI), the most commonly used tool for human neuroimaging. Through the course of this project we will investigate the links between neuroimaging signals and electrophysiology in the alert macaque in a variety of visual perceptual tasks. This will be an unparalleled opportunity to gain new insights into fMRI in an animal model that is the closest possible to the human. Our novel findings were obtained as a result of a new imaging technique developed in our laboratory, continuous dual-wavelength intrinsic-signal optical imaging, combined with electrode recordings, in alert behaving macaques. For the imaging, one wavelength is absorbed preferentially in oxygenated haemoglobin, thus monitoring blood oxygenation;the other wavelength, absorbed equally in oxygenated and deoxygenated haemoglobin, measures blood volume. The simultaneous electrode recordings give an electrophysiological measure of the underlying neuronal activity. The continuous recording allows us to distinguish between ongoing signals and stimulus-evoked responses. This technique will form the basis of the current project, giving a unique combination of tools to answer the questions at hand. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

Public Health Relevance

PROJECT NARRATIVE This project has two significant implications for public health. We propose to characterize a novel mechanism of brain arousal, thus shedding new light on processes of attention or alertness and their disorders (attention deficit disorder etc.). Further, our work challenges the current understanding of functional magnetic resonance imaging (fMRI), the most commonly used means of studying the human brain in clinical or scientific settings, and will therefore have major implications for the correct interpretation of this critically important medical tool. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Central Visual Processing Study Section (CVP)
Program Officer
Steinmetz, Michael A
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Ma, Ying; Shaik, Mohammed A; Kim, Sharon H et al. (2016) Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches. Philos Trans R Soc Lond B Biol Sci 371:
Chen, Brenda R; Kozberg, Mariel G; Bouchard, Matthew B et al. (2014) A critical role for the vascular endothelium in functional neurovascular coupling in the brain. J Am Heart Assoc 3:e000787
Lima, Bruss; Cardoso, Mariana M B; Sirotin, Yevgeniy B et al. (2014) Stimulus-related neuroimaging in task-engaged subjects is best predicted by concurrent spiking. J Neurosci 34:13878-91
Kozberg, Mariel G; Chen, Brenda R; DeLeo, Sarah E et al. (2013) Resolving the transition from negative to positive blood oxygen level-dependent responses in the developing brain. Proc Natl Acad Sci U S A 110:4380-5
Sirotin, Yevgeniy B; Cardoso, Mariana; Lima, Bruss et al. (2012) Spatial homogeneity and task-synchrony of the trial-related hemodynamic signal. Neuroimage 59:2783-97
Cardoso, Mariana M B; Sirotin, Yevgeniy B; Lima, Bruss et al. (2012) The neuroimaging signal is a linear sum of neurally distinct stimulus- and task-related components. Nat Neurosci 15:1298-306
McCaslin, Addason F H; Chen, Brenda R; Radosevich, Andrew J et al. (2011) In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling. J Cereb Blood Flow Metab 31:795-806
Das, Aniruddha; Sirotin, Yevgeniy B (2011) What could underlie the trial-related signal? A response to the commentaries by Drs. Kleinschmidt and Muller, and Drs. Handwerker and Bandettini. Neuroimage 55:1413-8; discussion 1419-22
Chen, Brenda R; Bouchard, Matthew B; McCaslin, Addason F H et al. (2011) High-speed vascular dynamics of the hemodynamic response. Neuroimage 54:1021-30
Sirotin, Yevgeniy B; Das, Aniruddha (2010) Zooming in on mouse vision. Nat Neurosci 13:1045-6

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